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Serum, Urine, and Fecal Metabolome Alterations in the Gut Microbiota in Response to Lifestyle Interventions in Pediatric Obesity: A Non-Randomized Clinical Trial.
Lee, Y, Cho, JY, Cho, KY
Nutrients. 2023;15(9)
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Paediatric obesity is linked to an increased risk of type 2 diabetes, hypertension, dyslipidaemia, and metabolic syndrome. Diverse evidence suggests that obesity is associated with alterations in the gut microbiota and its metabolites. The aim of this study was to understand the metabolic pathways underlying paediatric obesity and the effect of intervention, which could provide guidance for the treatment of obesity. This study was a non-randomised clinical trial which enrolled 50 children with obesity and 22 normal-weight children aged 7–18 years. Results showed that imbalances in microbiota and metabolites were associated with both obesity and response to the intervention. The most distinct metabolic alterations in the obese group were branched-chain amino acid and purine changes. Authors conclude that the findings of their study could be valuable for identifying novel targets and biomarkers for the treatment of obesity.
Abstract
Pediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + β acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.
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Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis.
Gómez-Pérez, AM, Ruiz-Limón, P, Salas-Salvadó, J, Vioque, J, Corella, D, Fitó, M, Vidal, J, Atzeni, A, Torres-Collado, L, Álvarez-Sala, A, et al
Gut microbes. 2023;15(1):2223339
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Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease. The aim of this study was to evaluate the changes in the microbiota associated with changes in biochemical markers of NAFLD/NASH after an intervention. This substudy was conducted in the frame of the PREDIMED-Plus study, a 6-year, multicentre, randomised clinical trial for primary prevention of cardiovascular disease (CVD) conducted in men aged 55–75 years and women aged 60–75 years with overweight or obesity and metabolic syndrome. Results showed a relationship between liver disease biochemical indexes changes and gut microbiota changes within a context of a Mediterranean lifestyle. In fact, two noninvasive scores for liver steatosis and liver fibrosis, usually used in clinical practice, could differentiate gut microbiota populations. Authors conclude that their findings highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.
Abstract
To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations. What You Need to KnowWhat is the context:Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD.What is new:Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB−4) in only one year. A relation between the changes in these scores and gut microbiota changes was found.What is the impact:The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD.
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An insight into the functional alterations in the gut microbiome of healthy adults in response to a multi-strain probiotic intake: a single arm open label trial.
Rodenes-Gavidia, A, Lamelas, A, Bloor, S, Hobson, A, Treadway, S, Haworth, J, Vijayakumar, V, Naghibi, M, Day, R, Chenoll, E
Frontiers in cellular and infection microbiology. 2023;13:1240267
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The human gut microbiota is a key mediator of host health and is known to affect many physiological processes, such as digestion, metabolism, immune function and inhibition of pathogen colonisation. The gut microbiome can be impacted by many extrinsic factors. The aim of this study was to assess both compositional and functional changes in the microbiome of healthy individuals using shotgun metagenomics following 8-weeks of daily multi-strain probiotic intake. This study was a single-arm open-label study which enrolled a total of 41 healthy adult males and females between 18 to 40 years old. Results showed that alpha- and beta-diversity of the faecal microbiota structure was not significantly altered in response to probiotic intake. However, significant changes were observed when functional genes were assessed. Abundance of certain genes involved in several functional pathways were also significantly altered. Additionally, there were no significant changes in stool frequency or consistency, faecal biochemistry, or breath tests of methane and hydrogen observed. Authors conclude that the findings of their study have the potential to provide insights into the underlying mechanisms of action of the 14-strain probiotic blend in healthy adults.
Abstract
BACKGROUND Probiotic supplements, by definition, provide a benefit to the host, but few studies have investigated the effect of probiotic supplements in healthy adult populations. PURPOSE The present, single arm, open label clinical trial, evaluated compositional and functional changes in the fecal microbiome of healthy adults after supplementation with a 14-strain probiotic. METHODS We analysed the effect of a 14-strain probiotic blend (Bacillus subtilis NCIMB 30223, Bifidobacterium bifidum NCIMB 30179, B. breve NCIMB 30180, B. infantis NCIMB 30181, B. longum NCIMB 30182, Lactobacillus helveticus NCIMB 30184, L. delbrueckii subsp. bulgaricus NCIMB 30186, Lacticaseibacillus paracasei NCIMB 30185, Lactiplantibacillus plantarum NCIMB 30187, Lacticaseibacillus rhamnosus NCIMB 30188, L. helveticus NCIMB 30224, Lactobacillus salivarius NCIMB 30225, Lactococcus lactis subsp. lactis NCIMB 30222, and Streptococcus thermophilus NCIMB 30189), on the faecal microbiota of healthy young adults (n=41) in a single arm study. The adults consumed 4 capsules daily of the 14 strain blend(8 billion colony forming units/day) for 8 weeks. Compositional and functional changes in faecal microbiota before and after supplementation were assessed using shotgun metagenomic sequencing. Fasting breath analysis, faecal biochemistry and bowel habits were also assessed. RESULTS In healthy adult participants, no significant changes to the overall alpha- or beta-diversity was observed after 8 weeks of multi-strain probiotic supplementation. However, in a simplified model that considered only time and individual differences, significant decreases (p < 0.05) in family Odoribacteraceae and Bacteroidaceae abundance and a significant increase (p < 0.05) in genus Megamonas abundance were observed. At a functional level, there were significant changes in functional gene abundance related to several functional pathways, including phenylalanine metabolism, O-antigen nucleotide sugar biosynthesis, bacterial chemotaxis, and flagellar assembly. No significant changes in stool form or frequency, fecal biochemistry, or methane and hydrogen breath tests were observed. CONCLUSION In healthy young adults, overall alpha- and beta-diversity did not change in response to probiotic intake even though modest compositional changes at the family and genus level were observed. However, at functional level, results identified changes in gene abundance for several functional pathways.
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A structured weight loss program increases gut microbiota phylogenetic diversity and reduces levels of Collinsella in obese type 2 diabetics: A pilot study.
Frost, F, Storck, LJ, Kacprowski, T, Gärtner, S, Rühlemann, M, Bang, C, Franke, A, Völker, U, Aghdassi, AA, Steveling, A, et al
PloS one. 2019;14(7):e0219489
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The global obesity epidemic is a major cause of the increase in type 2 diabetes mellitus (T2DM) and ensuing cardiovascular disease. The causes of obesity are complex ,and it has been shown that changes in the microbiome are associated with obesity. The microbiome can be altered through dietary intervention and weight loss. The aim of this open label pilot study was to investigate the microbiome of obese patients with T2DM during a weight loss programme. During the first six weeks the diet consisted of formula drink providing 800kcal per day, followed by nine weeks during which a regular diet of 1,200-1,500kcal per day was reintroduced, depending on the individuals’ needs. All participants lost weight continuously over the 15 weeks, from an average BMI of 39.6 at the start to 33.1 at the end of the programme. This was accompanied with an improvement in glucose metabolism, total and LDL cholesterol and uric acid levels, but not HDL cholesterol or triglycerides. All participants experienced changes in their microbiome towards greater diversity after the first six weeks of the low-calorie formula diet but these changes were partially reversed at the end of the study period at 15 weeks. A particular type of bacteria, Collinsella, which has been associated with poor metabolic health, was the only type found to remain reduced at the end of the 15 weeks, an 8.4-fold decrease. The authors hypothesise that this reduction in Collinsella may be associated with the improvement of metabolic factor in these patients at the end of the study.
Abstract
The global obesity epidemic constitutes a major cause of morbidity and mortality challenging public health care systems worldwide. Thus, a better understanding of its pathophysiology and the development of novel therapeutic options are urgently needed. Recently, alterations of the intestinal microbiome in the obese have been discussed as a promoting factor in the pathophysiology of obesity and as a contributing factor to related diseases such as type 2 diabetes and metabolic syndrome. The present pilot study investigated the effect of a structured weight loss program on fecal microbiota in obese type 2 diabetics. Twelve study subjects received a low-calorie formula diet for six weeks, followed by a nine week food reintroduction and stabilization period. Fecal microbiota were determined by 16S rRNA gene sequencing of stool samples at baseline, after six weeks and at the end of the study after fifteen weeks. All study subjects lost weight continuously throughout the program. Changes in fecal microbiota were most pronounced after six weeks of low-calorie formula diet, but reverted partially until the end of the study. However, the gut microbiota phylogenetic diversity increased persistently. The abundance of Collinsella, which has previously been associated with atherosclerosis, decreased significantly during the weight loss program. This study underlines the impact of dietary changes on the intestinal microbiome and further demonstrates the beneficial effects of weight loss on gut microbiota. Trial registration: ClinicalTrials.gov NCT02970838.